The effect of various psychotropic agents (phenothiazines, tricyclic antidepressants, MAO inhibitors, and lithium) on turnover of acetylcholine (ACh) in specific brain areas of rats and mice, will be studied using gas chromatography-mass spectrometry. The effect of these drugs on the activity of acetylcholinesterase and choline acetylase in these specific brain areas will also be investigated. Similar measurements will be done after administering drugs known to alter brain dopamine, GABA and phenylethylamine concentration in mouse and rat brain, because of the implications in the literature that dopamine, GABA and phenyl ethylamine might be interacting with ACh in certain mental disease states. We will attempt to determine whether the human blood platelet can be used as a model for the cholinergic nerve ending in man. The uptake and metabolism of choline (Ch) in platelets, platelet Ch and ACh concentration, and the activity of platelet cholinesterase will be studied in drug-free patients from various categories of psychiatric illness. Identical parameters will be measured in platelets of these patients after initiating appropriate drug treatment. Results will be compared with those seen in platelets obtained from rats treated by a similar drug regimen. Correlation of data with those obtained with in vivo turnover studies described in (i) will establish whether the platelet could be used as a model for the cholinergic nerve ending in humans. One can achieve efficient labelling of mouse brain ACh by supplying deuterium labelled Ch in the diet. This approach will be expanded and transport of plasma Ch, via brain ACh, cerebrospinal fluid (CSF) Ch will be analyzed in rabbits, because of the relative ease in obtaining CSF samples from this species. The effect of the psychotropic drugs on the rate of elimination of deuterium Ch will be evaluated in blood and CSF. Results will be compared with those obtained in the in vivo turnover studies in rats and mice (see I). These data will indicate whether kinetic analysis of Ch elimination from blood and CSF in animals fed with deuterated Ch may provide an indicator for Ch and ACh metabolism in the brain. (Text Abridged)